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  Heme Oxygenase-1 Drives Metaflammation and Insulin Resistance in Mouse and Man

Jais, A., Einwallner, E., Sharif, O., Gossens, K., Tsai-Hsiu Lu, T., Soyal, S. M., et al. (2014). Heme Oxygenase-1 Drives Metaflammation and Insulin Resistance in Mouse and Man. Cell, 158, 25-40.

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 Creators:
Jais, Alexander1, Author           
Einwallner, Elisa2, Author
Sharif, Omar, Author
Gossens, Klaus, Author
Tsai-Hsiu Lu, Tess1, Author           
Soyal, Selma M., Author
Medgyesi, David3, Author           
Neureiter, Daniel, Author
Paier-Pourani, Jamile, Author
Dalgaard, Kevin1, Author           
Duvigneau, J. Catharina, Author
Lindroos-Christensen, Josefine, Author
Zapf, Thea-Cristin, Author
Amann, Sabine, Author
Saluzzo, Simona, Author
Jantscher, Florian, Author
Stiedl, Patricia, Author
Todoric, Jelena, Author
Martins, Rui, Author
Oberkofler, Hannes, Author
Müller, Simone, AuthorHauser-Kronberger, Cornelia, AuthorKenner, Lukas, AuthorCasanova, Emilio, AuthorSutterlüty-Fall, Hedwig, AuthorBilban, Martin, AuthorMiller, Karl, AuthorKozlov, Andrey V., AuthorKrempler, Franz, AuthorKnapp, Sylvia, AuthorLumeng, Carey N., AuthorPatsch, Wolfgang, AuthorWagner, Oswald, AuthorPospisilik, J. Andrew1, Author           Esterbauer, Harald, Author more..
Affiliations:
1Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              
2Max Planck Society, ou_persistent13              
3Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243645              

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 Abstract: Obesity and diabetes affect more than half a billion individuals worldwide. Interestingly, the two conditions do not always coincide and the molecular determinants of "healthy" versus "unhealthy" obesity remain ill-defined. Chronic metabolic inflammation (metaflammation) is believed to be pivotal. Here, we tested a hypothesized anti-inflammatory role for heme oxygenase-1 (HO-1) in the development of metabolic disease. Surprisingly, in matched biopsies from "healthy" versus insulin-resistant obese subjects we find HO-1 to be among the strongest positive predictors of metabolic disease in humans. We find that hepatocyte and macrophage conditional HO-1 deletion in mice evokes resistance to diet-induced insulin resistance and inflammation, dramatically reducing secondary disease such as steatosis and liver toxicity. Intriguingly, cellular assays show that HO-1 defines prestimulation thresholds for inflammatory skewing and NF-κB amplification in macrophages and for insulin signaling in hepatocytes. These findings identify HO-1 inhibition as a potential therapeutic strategy for metabolic disease.

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Language(s): eng - English
 Dates: 2014-07-03
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 701145
 Degree: -

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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 158 Sequence Number: - Start / End Page: 25 - 40 Identifier: -